The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
Peripheral Stimulations (Transcutaneous Electrical Nerve Stimulation [TENS], Peripheral Nerve Stimulation [PNS], and Nerve Root Stimulation [NRS])
The guideline developers cannot draw any conclusion for PNS and NRS. Even for TENS, it is difficult to come to conclusive recommendations. The total number of patients with ascertained neuropathic pain was only some 200, with diseases, comparators, and results varying considerably from study to study. Stimulation parameters also vary considerably between the studies, using different pulse waveforms and a wide range of frequencies, not to mention number and duration of the sessions. In conclusion, standard high-frequency TENS is possibly better than placebo (level C) though probably worse than acupuncture-like or any other kind of electrical stimulation (level B).
Refer to Table 1 in the original guideline document for summary of efficacy and safety of peripheral stimulations.
Spinal Cord Stimulation (SCS)
The guideline developers found level B evidence for the effectiveness of SCS in failed back surgery syndrome (FBSS) and complex regional pain syndrome, type I (CRPS I). The available evidence is also positive for CRPS type II, peripheral nerve injury, diabetic neuropathy, post-herpetic neuralgia (PHN), brachial plexus lesion, amputation (stump and phantom pains), and partial spinal cord injury, but still requires confirmatory comparative trials before the use of SCS can be unreservedly recommended in these conditions.
Refer to Table 2 in the original guideline document for summary of efficacy and safety of SCS.
Deep Brain Stimulation (DBS)
For the use of DBS there is weak positive evidence in peripheral neuropathic pain including pain after amputation and facial pain (expert opinion requiring confirmatory trials). In central post-stroke pain (CPSP), DBS results are equivocal and require further comparative trials.
Refer to Tables 3, 4, 5, and 6 in the original guideline document for summary of efficacy and safety of DBS.
Motor Cortex Stimulation (MCS)
There is level C evidence (two convincing class III studies, 15 to 20 convergent class IV series) that MCS is useful in 50 to 60% of patients with CPSP and central or peripheral facial neuropathic pain, with small risk of medical complications. The evidence about any other condition remains insufficient.
Refer to Tables 7 and 8 in the original guideline document for summary of efficacy and safety of MCS in CPSP and facial pain, respectively.
Repetitive Transcranial Magnetic Stimulation (rTMS)
There is moderate evidence that rTMS of the motor cortex, using a figure-of-eight coil and high frequency (5 to 20 Hz) induces significant pain relief in CPSP and several other neuropathic pain conditions (level B). However, because the effect is modest and short-lasting, rTMS should not be used as the sole treatment in chronic neuropathic pain. It may be proposed for short-lasting pains or to identify suitable candidates for an epidural implant (MCS). In contrast, in the same pain conditions, low-frequency rTMS is probably ineffective (level B).
Refer to Tables 9 and 10 in the original guideline document for summary of efficacy and safety of rTMS.
Definitions:
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations >for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
